LEP and obesity due to melanocortin 4 receptor deficiency: SM is a high-affinity ligand for MC4R, described in 2021 as an MC4R-SM structure complex [37], and has been approved in 2020 by the U.S. Food and Drug Administration (FDA) for the treatment of some forms of rare monogenetic obesity due to mutations in the melanocortin–leptin pathway, namely, pro-opiomelanocortin (POMC) deficiency, proprotein subtilisin/kexin type 1 (PCSK1) deficiency, and leptin receptor (LEPR) deficiency [43].